**2. Cardiovascular risk**

#### **2.1 Cardiovascular risk factors in diabetes**

The concept of cardiovascular risk began to be of interest in the 1930s. Studies of cardiovascular disease epidemiology and its causes began in the 1950s, with Framingham Heart Study being one of the first. This extended program has demonstrated the existence of multiple CVR factors over the years, introducing in the literature and medical concept the term "risk factor". Among the study's first results, high blood pressure, hypercholesterolemia, and smoking are considered traditional, classic, risk factors. Subsequently, Framingham study and other epidemiological studies, have identified other risk factors, including obesity, diabetes, dyslipidemia, sedentary lifestyle. Thus diabetes is associated with a 2- to 3-fold increase in the risk of developing CVD and glucose intolerance with a 1.5-fold increase [5–7]. In addition to hyperglycemia, diabetes, mainly T2DM, is accompanied by other cardiovascular risk factors, within the metabolic syndrome: insulin resistance, abdominal obesity, atherogenic dyslipidemia (hypertriglyceridemia, low HDL-C (High-density lipoprotein cholesterol), LDL-C (low density lipoprotein cholesterol particles), remnant lipoproteins, postprandial hyperlipidemia), high blood pressure, prothrombotic, proinflammatory and oxidative stress state, microalbuminuria, non-alcoholic fatty liver disease [8].

High blood pressure increases 2–4 times the risk of CVD, kidney and death, atherogenic dyslipidemia induces a residual CVR, even under statin treatment and LDL-C control and abdominal obesity, as a component of metabolic syndrome, significantly increases the risk of coronary heart disease, stroke and death [9–11].

#### **2.2 Cardiovascular risk in T2DM**

Overall, people with T2DM have 2 to 4 times increased risk of cardiovascular morbidity and mortality than individuals without diabetes. This risk increases with the increase of fasting glycaemia since the stages of prediabetes. The risk for CAD is rising by 160%, for ischemic heart disease by 127%, for stroke by 56%, for CVD

**279**

*Cardiovascular Risk/Disease in Type 2 Diabetes Mellitus DOI: http://dx.doi.org/10.5772/intechopen.97422*

women, compared to those without diabetes [5].

factor interventions in these clusters of patients. [12]

any other additional risk factor, and

T1DM of >20-year duration [12].

with DM duration <10 years, without other risk factors,

proteinuria [12].

risk factor for CVD:

kidney disease) [15].

risk for HF hospitalization [16].

**2.3 Cardiovascular risk assessment**

death by 132% [4], and for HF is 2–4 times higher in men and five times higher in

events is more significant in women, at younger ages, in long-standing DM and in the presence of microvascular complications, mainly renal disease or

differentiated based on the presence of other CVR factors or overt CVD.

Epidemiological studies have revealed that the excess relative risk of vascular

Although T2DM was initially considered a "cardiovascular risk equivalent" [12–14], it has since been shown that CVR, mainly CAD risk, is not similar for all persons with diabetes, but is highly heterogeneous. Thus, the CVR should be

For T1DM, The Swedish National Diabetes Register has shown actual results in CVD and CV death prevalence. [13] For T1DM, 27,195 patients were stratified by age and sex. Early-onset at 1–10 years of age was correlated with an HR (hazard ratio) of 7.38 for CV mortality, 30.95 for acute myocardial infarction (MI), and 12.9 for heart failure (HF). Progress of T1DM between 1 and 10 years of age resulted in a loss of 17.7 years of life in women and 14.2 years in men. [13] Notwithstanding, T2DM is more common than T1DM.These results confirm the loss of years of life in both populations, which is more severe in the younger patients and in young-onset female individuals with T2DM, highlighting the need for early and intensive risk-

The European Society of Cardiology stratifies the CVR into three risk categories, including T1DM, considering that presence of DM overall represents a significant

• **moderate:** young patients (T1DM aged <35 years or T2DM aged <50 years),

• **high:** patients with DM duration ≥10 years without target organ damage plus

• **very high:** patients with DM and established CVD, or further target organ damage (proteinuria, renal impairment defined as eGFR <30 mL/min/1.73 m<sup>2</sup>

left ventricular hypertrophy, or retinopathy), or three or more major risk factors (age, hypertension, dyslipidemia, smoking, obesity), or early-onset

The American Association of Clinical Endocrinologists (AACE) stratifies the CVR into three levels: **high** (DM without other CVR factors), **very high** (DM with at least one CVR factor), and **extreme risk** (overt CVD in those with DM, chronic

T2DM is reputed as an independent risk factor for the development of HF. Higher levels of glycated hemoglobin A1c (HbA1c) in T2DM patients have been associated with significantly more incident HF cases than in patients with T2DM and lower HbA1c levels. The incidence is even higher in patients with established CAD, in which each 1% increase in HbA1c level was associated with a 36% increased

A rational and successful approach to reducing the CVR involves stratifying risk and the periodic evaluation of the outcomes. Accurate CVD risk estimation in people with T2DM without established CVD can identify patients at high risk of developing CVD and can thus be used to adapt the intensity and complexity of

,

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

place a heavy burden on health care systems.

**2.1 Cardiovascular risk factors in diabetes**

**2.2 Cardiovascular risk in T2DM**

**2. Cardiovascular risk**

depression) [1].

diameter, compared to people without DM. The pathogenic complex is influenced by genetic factors, age, personal history and a pro-risk lifestyle (unhealthy eating, sedentary lifestyle, smoking, sleep disorders, psychosocial stress and

cerebrovascular disease (CBV). A particular complication is heart failure (HF). The pathogenic mechanisms of micro-and macro-angiopathy are extremely complex, with multiple interactions at the molecular-cellular and vascular-organic level. Although all complications declined in the last decades, the most significant decreases in diabetes-related complications occurred for heart attack and stroke, especially for people aged 75 years and older. The CVD risk and mortality rate has declined in both the general population [2] and the people with diabetes [3]. However, diabetes, mainly T2DM, continues to be an important generator of cardiovascular disease. As the number of patients with diabetes is predicted to increase, reaching 700 million in 2045 [4], it is expected that the number of people with CVD will also increase. Thus, these major diabetes complications continue to

The concept of cardiovascular risk began to be of interest in the 1930s. Studies of cardiovascular disease epidemiology and its causes began in the 1950s, with Framingham Heart Study being one of the first. This extended program has demonstrated the existence of multiple CVR factors over the years, introducing in the literature and medical concept the term "risk factor". Among the study's first results, high blood pressure, hypercholesterolemia, and smoking are considered traditional, classic, risk factors. Subsequently, Framingham study and other epidemiological studies, have identified other risk factors, including obesity, diabetes, dyslipidemia, sedentary lifestyle. Thus diabetes is associated with a 2- to 3-fold increase in the risk of developing CVD and glucose intolerance with a 1.5-fold increase [5–7]. In addition to hyperglycemia, diabetes, mainly T2DM, is accompanied by other cardiovascular risk factors, within the metabolic syndrome: insulin resistance, abdominal obesity, atherogenic dyslipidemia

(hypertriglyceridemia, low HDL-C (High-density lipoprotein cholesterol), LDL-C (low density lipoprotein cholesterol particles), remnant lipoproteins, postprandial hyperlipidemia), high blood pressure, prothrombotic, proinflammatory and oxidative stress state, microalbuminuria, non-alcoholic fatty liver disease [8]. High blood pressure increases 2–4 times the risk of CVD, kidney and death, atherogenic dyslipidemia induces a residual CVR, even under statin treatment and LDL-C control and abdominal obesity, as a component of metabolic syndrome, significantly increases the risk of coronary heart disease, stroke and death [9–11].

Overall, people with T2DM have 2 to 4 times increased risk of cardiovascular morbidity and mortality than individuals without diabetes. This risk increases with the increase of fasting glycaemia since the stages of prediabetes. The risk for CAD is rising by 160%, for ischemic heart disease by 127%, for stroke by 56%, for CVD

The macrovascular complications mainly refer to the atherosclerotic cardiovascular disease, represented by coronary artery disease (acute and chronic

coronary syndrome) (CAD), chronic peripheral artery disease (PAD) and

**278**

death by 132% [4], and for HF is 2–4 times higher in men and five times higher in women, compared to those without diabetes [5].

Epidemiological studies have revealed that the excess relative risk of vascular events is more significant in women, at younger ages, in long-standing DM and in the presence of microvascular complications, mainly renal disease or proteinuria [12].

Although T2DM was initially considered a "cardiovascular risk equivalent" [12–14], it has since been shown that CVR, mainly CAD risk, is not similar for all persons with diabetes, but is highly heterogeneous. Thus, the CVR should be differentiated based on the presence of other CVR factors or overt CVD.

For T1DM, The Swedish National Diabetes Register has shown actual results in CVD and CV death prevalence. [13] For T1DM, 27,195 patients were stratified by age and sex. Early-onset at 1–10 years of age was correlated with an HR (hazard ratio) of 7.38 for CV mortality, 30.95 for acute myocardial infarction (MI), and 12.9 for heart failure (HF). Progress of T1DM between 1 and 10 years of age resulted in a loss of 17.7 years of life in women and 14.2 years in men. [13] Notwithstanding, T2DM is more common than T1DM.These results confirm the loss of years of life in both populations, which is more severe in the younger patients and in young-onset female individuals with T2DM, highlighting the need for early and intensive riskfactor interventions in these clusters of patients. [12]

The European Society of Cardiology stratifies the CVR into three risk categories, including T1DM, considering that presence of DM overall represents a significant risk factor for CVD:


The American Association of Clinical Endocrinologists (AACE) stratifies the CVR into three levels: **high** (DM without other CVR factors), **very high** (DM with at least one CVR factor), and **extreme risk** (overt CVD in those with DM, chronic kidney disease) [15].

T2DM is reputed as an independent risk factor for the development of HF. Higher levels of glycated hemoglobin A1c (HbA1c) in T2DM patients have been associated with significantly more incident HF cases than in patients with T2DM and lower HbA1c levels. The incidence is even higher in patients with established CAD, in which each 1% increase in HbA1c level was associated with a 36% increased risk for HF hospitalization [16].
